Pharmaceutical compositions often include polymers to achieve specific desired therapeutic effects, including for use as coating agents, as film-formers, as rate-controlling polymers for sustained or controlled release, as stabilizing agents, as suspending agents, as tablet binders, and as viscosity-increasing agents.
Hydroxypropyl methyl cellulose acetate succinate (HPMCAS) was originally developed as an enteric polymer for pharmaceutical dosage forms and for providing halation-preventing layers on photographic films. See Onda et al., U.S. Pat. No. 4,226,981. Enteric polymers are those that remain intact in the acidic environment of the stomach; dosage forms coated with such polymers protect the active agent from inactivation or degradation in the acidic environment and/or reduce irritation of the stomach by the active agent. HPMCAS is currently commercially available from Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan), known by the trade name “AQOAT.” Shin-Etsu manufactures three grades of AQOAT that have different combinations of substituent levels to provide enteric protection at various pH levels. The AS-LF and AS-LG grades (the “F” standing for fine and the “G” standing for granular) provide enteric protection up to a pH of 5.5. The AS-MF and AS-MG grades provide enteric protection up to a pH of 6.0, while the AS-HF and AS-HG grades provide enteric protection up to a pH of 6.8. Shin-Etsu gives the following specifications for these three grades of AQOAT polymers:
TABLE 1Composition of Shin-Etsu'sAQOAT Polymers (wt %)SubstituentL GradesM GradesH GradesMethoxyl Content20.0-24.021.0-25.022.0-26.0Hydroxypropoxyl5.0-9.05.0-9.0 6.0-10.0ContentAcetyl Content5.0-9.0 7.0-11.010.0-14.0Succinoyl14.0-18.010.0-14.04.0-8.0
While pharmaceutical formulations of low-solubility active agents and HPMCAS have proven effective, the AQOAT polymers manufactured by Shin-Etsu provide only a limited selection of properties for forming such formulations.
What is desired are HPMCAS polymers designed specifically for improving the dissolved concentration of an active agent and the stability of active agents in the composition. Additionally, there is a need to adjust the properties of polymers used in pharmaceutical compositions for numerous applications, including concentration-enhancement and controlled release applications.